Identification

Name
Acenocoumarol
Accession Number
DB01418
Description

Acenocoumarol is a coumarin derivative used as an anticoagulant. Coumarin derivatives inhibit the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of vitamin K-dependent clotting factors, II, VII, IX and X, and interferes with coagulation.6 Hematocrit, hemoglobin, international normalized ratio and liver panel should be monitored. Patients on acenocoumarol are prohibited from giving blood.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 353.3255
Monoisotopic: 353.089937217
Chemical Formula
C19H15NO6
Synonyms
  • 3-(alpha-(4'-Nitrophenyl)-beta-acetylethyl)-4-hydroxycoumarin
  • 3-(alpha-(p-Nitrophenol)-beta-acetylethyl)-4-hydroxycoumarin
  • 3-(alpha-Acetonyl-4-nitrobenzyl)-4-hydroxycoumarin
  • 3-(alpha-Acetonyl-p-nitrobenzyl)-4-hydroxycoumarin
  • 3-(alpha-p-Nitrophenyl-beta-acetylethyl)-4-hydroxycoumarin
  • 4-Hydroxy-3-(1-(4-nitrophenyl)-3-oxobutyl)-2H-1-benzopyran-2-one
  • 4-Hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
  • Acenocoumarin
  • Acénocoumarol
  • Acenocoumarol
  • Acenocoumarolum
  • Acenocumarol
  • Acenocumarolo
  • Acenokumarin
  • Nicoumalone
  • Nicumalon
  • Nitrophenylacetylethyl-4-hydroxycoumarine
  • Nitrovarfarian
  • Nitrowarfarin

Pharmacology

Indication

For the treatment and prevention of thromboembolic diseases. More specifically, it is indicated for the prevention of cerebral embolism, deep vein thrombosis, pulmonary embolism, thromboembolism in infarction and transient ischemic attacks. It is used for the treatment of deep vein thrombosis and myocardial infarction.

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Acenocoumarol inhibits the reduction of vitamin K by vitamin K reductase. This prevents carboxylation of certain glutamic acid residues near the N-terminals of clotting factors II, VII, IX and X, the vitamin K-dependent clotting factors. Glutamic acid carboxylation is important for the interaction between these clotting factors and calcium. Without this interaction, clotting cannot occur. Both the extrinsic (via factors VII, X and II) and intrinsic (via factors IX, X and II) are affected by acenocoumarol.

Mechanism of action

Acenocoumarol inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent clotting factors, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited resulting in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.

TargetActionsOrganism
AVitamin K epoxide reductase complex subunit 1
inhibitor
Humans
Absorption

Rapidly absorbed orally with greater than 60% bioavailability. Peak plasma levels are attained 1 to 3 hours following oral administration.

Volume of distribution

The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses < or = 20 microg/kg and 88 ml/kg for doses > 20 microg/kg respectively

Protein binding

98.7% protein bound, mainly to albumin

Metabolism

Extensively metabolized in the liver via oxidation forming two hydroxy metabolites and keto reduction producing two alcohol metabolites. Reduction of the nitro group produces an amino metabolite which is further transformed to an acetoamido metabolite. Metabolites do not appear to be pharmacologically active.

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Route of elimination

Mostly via the kidney as metabolites

Half-life

8 to 11 hours.

Clearance
Not Available
Adverse Effects
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Toxicity

The onset and severity of the symptoms are dependent on the individual's sensitivity to oral anticoagulants, the severity of the overdosage, and the duration of treatment. Bleeding is the major sign of toxicity with oral anticoagulant drugs. The most frequent symptoms observed are: cutaneous bleeding (80%), haematuria (with renal colic) (52%), haematomas, gastrointestinal bleeding, haematemesis, uterine bleeding, epistaxis, gingival bleeding and bleeding into the joints. Further symptoms include tachycardia, hypotension, peripheral circulatory disorders due to loss of blood, nausea, vomiting, diarrhoea and abdominal pains.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Acenocoumarol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C9CYP2C9*2(T;T) / (C;T)T AlleleEffect Directly StudiedThe presence of this polymorphism in CYP2C9 is associated with reduction in acenocoumarol metabolism.Details
Cytochrome P450 2C9CYP2C9*3(C;C) / (A;C)C AlleleEffect Directly StudiedThe presence of this polymorphism in CYP2C9 is associated with reduction in acenocoumarol metabolism.Details
Vitamin K epoxide reductase complex subunit 1---(A;A) / (A;G)G > AADR Directly StudiedThe presence of this single nucleotide polymorphism in VKORC1 is associated with reduction in acenocoumarol metabolism and increased risk of drug-related hemorrhage.Details
Cytochrome P450 2C9CYP2C9*2(T;T) / (C;T)T AlleleEffect Directly StudiedPatients with this polymorphism in CYP2C9 may be at a higher risk of developing drug-related hemorrhage or thrombosis when treated with acenocoumarol.Details
Cytochrome P450 2C9CYP2C9*3(C;C) / (A;C)C AlleleEffect Directly StudiedPatients with this polymorphism in CYP2C9 may be at a higher risk of developing drug-related hemorrhage or thrombosis when treated with acenocoumarol.Details
Cytochrome P450 2C9CYP2C9*6Not Available818delAEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*15Not Available485C>AEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*25Not Available353_362delAGAAATGGAAEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*35Not Available374G>T / 430C>TEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*4Not Available1076T>CEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*5Not Available1080C>GEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*8Not Available449G>AEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*11Not Available1003C>TEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*12Not Available1465C>TEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*13Not Available269T>CEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*14Not Available374G>AEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*16Not Available895A>GEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*18Not Available1075A>C / 1190A>C  … show all Effect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*26Not Available389C>GEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*28Not Available641A>TEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*30Not Available1429G>AEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details
Cytochrome P450 2C9CYP2C9*33Not Available395G>AEffect InferredPoor drug metabolizer, associated with lower dose requirement.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Acenocoumarol can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Acenocoumarol can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Acenocoumarol.
AbirateroneThe serum concentration of Acenocoumarol can be increased when it is combined with Abiraterone.
AcalabrutinibThe serum concentration of Acenocoumarol can be increased when it is combined with Acalabrutinib.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with Acenocoumarol.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Acemetacin is combined with Acenocoumarol.
AcetaminophenThe metabolism of Acenocoumarol can be increased when combined with Acetaminophen.
AcetazolamideThe serum concentration of Acenocoumarol can be increased when it is combined with Acetazolamide.
Acetic acidThe risk or severity of bleeding can be increased when Acetic acid is combined with Acenocoumarol.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
  • Ensure consistent Vitamin K intake. Changes in vitamin K intake may impact coagulation. Foods containing vitamin K include spinach, kale, and swiss chard.
  • Exercise caution with St. John's Wort.

Products

International/Other Brands
Ascumar (Star) / Mini-sintrom
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
SintromTabletOralPaladin Labs Inc1962-12-31Not applicableCanada flag
SintromTabletOralPaladin Labs Inc1957-12-31Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
B01AA07 — Acenocoumarol
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Coumarins and derivatives
Sub Class
Hydroxycoumarins
Direct Parent
4-hydroxycoumarins
Alternative Parents
1-benzopyrans / Nitrobenzenes / Nitroaromatic compounds / Pyranones and derivatives / Vinylogous acids / Heteroaromatic compounds / Lactones / Ketones / Propargyl-type 1,3-dipolar organic compounds / Oxacyclic compounds
show 5 more
Substituents
1-benzopyran / 4-hydroxycoumarin / Allyl-type 1,3-dipolar organic compound / Aromatic heteropolycyclic compound / Benzenoid / Benzopyran / C-nitro compound / Carbonyl group / Heteroaromatic compound / Hydrocarbon derivative
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
C-nitro compound, methyl ketone, hydroxycoumarin (CHEBI:53766)

Chemical Identifiers

UNII
I6WP63U32H
CAS number
152-72-7
InChI Key
VABCILAOYCMVPS-UHFFFAOYSA-N
InChI
InChI=1S/C19H15NO6/c1-11(21)10-15(12-6-8-13(9-7-12)20(24)25)17-18(22)14-4-2-3-5-16(14)26-19(17)23/h2-9,15,22H,10H2,1H3
IUPAC Name
4-hydroxy-3-[1-(4-nitrophenyl)-3-oxobutyl]-2H-chromen-2-one
SMILES
CC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=CC=CC=C2OC1=O

References

Synthesis Reference

Stoll, W. and Litvan, F.; U.S. Patent 2,648,682; August 11,1953; assigned to J.R. Geigy A.G., Switzerland.

General References
  1. Cesar JM, Garcia-Avello A, Navarro JL, Herraez MV: Aging and oral anticoagulant therapy using acenocoumarol. Blood Coagul Fibrinolysis. 2004 Oct;15(8):673-6. [PubMed:15613922]
  2. Lengyel M: [Warfarin or acenocoumarol is better in the anticoagulant treatment of chronic atrial fibrillation?]. Orv Hetil. 2004 Dec 26;145(52):2619-21. [PubMed:15724697]
  3. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  4. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. [PubMed:16611310]
  5. Girard P, Nony P, Erhardtsen E, Delair S, Ffrench P, Dechavanne M, Boissel JP: Population pharmacokinetics of recombinant factor VIIa in volunteers anticoagulated with acenocoumarol. Thromb Haemost. 1998 Jul;80(1):109-13. [PubMed:9684795]
  6. Danziger J: Vitamin K-dependent proteins, warfarin, and vascular calcification. Clin J Am Soc Nephrol. 2008 Sep;3(5):1504-10. doi: 10.2215/CJN.00770208. Epub 2008 May 21. [PubMed:18495950]
Human Metabolome Database
HMDB0015487
KEGG Drug
D07064
PubChem Compound
54676537
PubChem Substance
46507631
ChemSpider
10443441
RxNav
154
ChEBI
53766
ChEMBL
CHEMBL397420
Therapeutic Targets Database
DAP000772
PharmGKB
PA452632
Wikipedia
Acenocoumarol
AHFS Codes
  • 20:12.04.08 — Coumarin Derivatives
MSDS
Download (126 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAcute Pulmonary Embolism1
4CompletedTreatmentAortic Valve Stenosis / Stroke1
4CompletedTreatmentCervical Artery Dissection1
4CompletedTreatmentDisorders, Blood Coagulation1
4CompletedTreatmentVenous Thromboembolism1
4Unknown StatusPreventionCerebrovascular Accident / Prosthetic Cardiac Valve Thrombosis / Prosthetic Valve Malfunction1
4Unknown StatusTreatmentAtrial Fibrillation (AF) / Stroke1
3Active Not RecruitingPreventionAtrial Fibrillation (AF) / Flutter, Atrial / Intracranial Hemorrhage, Hypertensive / Intracranial Hemorrhages / Intraventricular Hemorrhage / Microhaemorrhage / Small Vessel Cerebrovascular Disease / Subarachnoid Hemorrhage / Subdural haematoma1
3CompletedTreatmentAntiphospholipid Syndrome1
3CompletedTreatmentAtrial Fibrillation (AF)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral
TabletOral1 MG
TabletOral4 MG
Prices
Unit descriptionCostUnit
Sintrom 4 mg Tablet1.6USD tablet
Sintrom 1 mg Tablet0.51USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)196-199Merck Index 23
water solubilitypractically insolubleMSDS
logP1.98SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0106 mg/mLALOGPS
logP2.53ALOGPS
logP2.68ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)5.79ChemAxon
pKa (Strongest Basic)-6.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area109.42 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity94.18 m3·mol-1ChemAxon
Polarizability34.35 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.7518
Blood Brain Barrier+0.5765
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.6031
P-glycoprotein inhibitor INon-inhibitor0.7078
P-glycoprotein inhibitor IINon-inhibitor0.843
Renal organic cation transporterNon-inhibitor0.8944
CYP450 2C9 substrateNon-substrate0.6256
CYP450 2D6 substrateNon-substrate0.8936
CYP450 3A4 substrateSubstrate0.6267
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.831
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7492
Ames testAMES toxic0.6954
CarcinogenicityNon-carcinogens0.7015
BiodegradationNot ready biodegradable0.9403
Rat acute toxicity2.7869 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6326
hERG inhibition (predictor II)Non-inhibitor0.9347
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Vitamin-k-epoxide reductase (warfarin-sensitive) activity
Specific Function
Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the...
Gene Name
VKORC1
Uniprot ID
Q9BQB6
Uniprot Name
Vitamin K epoxide reductase complex subunit 1
Molecular Weight
18234.3 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Bodin L, Verstuyft C, Tregouet DA, Robert A, Dubert L, Funck-Brentano C, Jaillon P, Beaune P, Laurent-Puig P, Becquemont L, Loriot MA: Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity. Blood. 2005 Jul 1;106(1):135-40. Epub 2005 Mar 24. [PubMed:15790782]
  3. Gonzalez-Conejero R, Corral J, Roldan V, Ferrer F, Sanchez-Serrano I, Sanchez-Blanco JJ, Marin F, Vicente V: The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol. J Thromb Haemost. 2007 Aug;5(8):1701-6. Epub 2007 May 21. [PubMed:17596133]
  4. Montes R, Ruiz de Gaona E, Martinez-Gonzalez MA, Alberca I, Hermida J: The c.-1639G > A polymorphism of the VKORC1 gene is a major determinant of the response to acenocoumarol in anticoagulated patients. Br J Haematol. 2006 Apr;133(2):183-7. [PubMed:16611310]
  5. Rettie AE, Farin FM, Beri NG, Srinouanprachanh SL, Rieder MJ, Thijssen HH: A case study of acenocoumarol sensitivity and genotype-phenotype discordancy explained by combinations of polymorphisms in VKORC1 and CYP2C9. Br J Clin Pharmacol. 2006 Nov;62(5):617-20. Epub 2006 Jul 21. [PubMed:16869821]
  6. Schalekamp T, Brasse BP, Roijers JF, Chahid Y, van Geest-Daalderop JH, de Vries-Goldschmeding H, van Wijk EM, Egberts AC, de Boer A: VKORC1 and CYP2C9 genotypes and acenocoumarol anticoagulation status: interaction between both genotypes affects overanticoagulation. Clin Pharmacol Ther. 2006 Jul;80(1):13-22. [PubMed:16815313]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [PubMed:18021343]
  2. Thijssen HH, Ritzen B: Acenocoumarol pharmacokinetics in relation to cytochrome P450 2C9 genotype. Clin Pharmacol Ther. 2003 Jul;74(1):61-8. doi: 10.1016/S0009-9236(03)00088-2. [PubMed:12844136]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [PubMed:18021343]
  3. Acenocoumarol monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [PubMed:18021343]
  3. Acenocoumarol monograph [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [PubMed:16372822]
  2. Morales-Molina JA, Arrebola MA, Robles PA, Mangana JC: Possible interaction between topical terbinafine and acenocoumarol. Ann Pharmacother. 2009 Nov;43(11):1911-2. doi: 10.1345/aph.1M299. Epub 2009 Oct 20. [PubMed:19843835]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Fitos I, Visy J, Simonyi M, Hermansson J: Stereoselective distribution of acenocoumarol enantiomers in human plasma: chiral chromatographic analysis of the ultrafiltrates. Chirality. 1993;5(5):346-9. [PubMed:8398591]
  2. Fitos I, Visy J, Magyar A, Kajtar J, Simonyi M: Inverse stereoselectivity in the binding of acenocoumarol to human serum albumin and to alpha 1-acid glycoprotein. Biochem Pharmacol. 1989 Jul 15;38(14):2259-62. [PubMed:2751692]
  3. Otagiri M, Fleitman JS, Perrin JH: Investigations into the binding of phenprocoumon to albumin using fluorescence spectroscopy. J Pharm Pharmacol. 1980 Jul;32(7):478-82. [PubMed:6105183]
Kind
Protein
Organism
Humans
Pharmacological action
No
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Fitos I, Visy J, Simonyi M, Hermansson J: Stereoselective distribution of acenocoumarol enantiomers in human plasma: chiral chromatographic analysis of the ultrafiltrates. Chirality. 1993;5(5):346-9. [PubMed:8398591]
  2. Fitos I, Visy J, Magyar A, Kajtar J, Simonyi M: Inverse stereoselectivity in the binding of acenocoumarol to human serum albumin and to alpha 1-acid glycoprotein. Biochem Pharmacol. 1989 Jul 15;38(14):2259-62. [PubMed:2751692]
  3. Hazai E, Visy J, Fitos I, Bikadi Z, Simonyi M: Selective binding of coumarin enantiomers to human alpha1-acid glycoprotein genetic variants. Bioorg Med Chem. 2006 Mar 15;14(6):1959-65. Epub 2005 Nov 15. [PubMed:16290938]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Saraeva RB, Paskaleva ID, Doncheva E, Eap CB, Ganev VS: Pharmacogenetics of acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 gene polymorphisms and dose requirements. J Clin Pharm Ther. 2007 Dec;32(6):641-9. [PubMed:18021343]

Drug created on July 24, 2007 02:32 / Updated on October 27, 2020 11:13

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